The availability of oral DMTs, improved treatment optimization in MS. However, the impact of their different mechanism of action on disability accrual and relapses, must be further defined.

This retrospective observational cohort included treatment-naive patients from the Italian MS registry, starting fingolimod (FIN), teriflunomide (TER) or dimethyl fumarate (DMF), followed-up for 5 years, with ≥1 EDSS per year. Trajectories of disability and relapse-rate were evaluated  by applying a longitudinal model for repeated measures with an autoregressive variance-covariance structure.  The estimated values were adjusted for gender, age, clinical onset (monofocal/multifocal), time to first DMT, ARR, relapses and EDSS before DMTs. Changes of EDSS and relapse-rate were evaluated within and between FIN, TER and DMF at each semester for 5 years.

171 FIN, 117 TER and 182 DMF patients were selected. Disability trajectories of the groups, paired for the listed covariates, showed a similar pattern over time. However, FIN patients showed a significant increase in EDSS from the 2^nd semester (0.76, p=0.0007), while in DMF and TER, EDSS variations were significant from the 3^rd and 4^th semester respectively. The mean estimated delta-EDSS differences between DMF and FIN decreased, not significantly over time, while differences between TER and FIN increased (from -0.51 to -0.70), reaching statistical significance in the 4^th year (p=0.043). Trajectories of relapse-rate showed a significant reduction in each group immediately after the treatment start. Estimated changes of relapse-rate at each 12-month period were all significantly (p<0.0001) higher in both DMF and TER compared to FIN group.

In our real-life cohort, the three oral DMTs showed a similar long-term effect on disability progression, while FIN proved to be more effective on relapse-rate.